Memory B Cell Repertoire for Recognition of Evolving SARS-CoV-2 Spike by P. Tong et al
Memory B cell reserves can generate protective antibodies against repeated SARS-CoV-2 infections, but with unknown reach from original infection to antigenically drifted variants. We have sorted 216 spike-specific antibodies from 19 COVID-19 convalescent subjects. We charted memory B cell receptor-encoded antibodies by ELISA-and cell-based competition assay and found 7 major antibody competition groups against epitopes recurrently targeted across individuals. We included 15 published and newly determined structures of antibody-S complexes identified corresponding epitopic regions by cryo-EM. Group assignment correlated with cross-CoV-reactivity breadth, neutralization potency, and convergent antibody signatures. We used cell-based assay to test our well characterized cluster of antibodies binding to emerging SARS-CoV-2 variants. The variant of concern-- B.1.1.7, B.1.351 and P.1 largely escaped antibody groups tightly associated with the most potent neutralizing activity targeting SARS-CoV-2 N terminal domain and receptor binding domain of spike. Antibodies recognition to the S2 subdomain of spike is least affected. Escape was incomplete as some antibodies within variant-escaped competition groups (defined by original S binding) retained variant binding—suggesting the protective importance of otherwise-redundant original-virus recognition toward evolving virus. The results furnish a global atlas of S-specific memory B cell repertoires and illustrate properties driving viral escape and conferring robustness against emerging SARS-CoV-2 variants.